Direct biochemical and neuropharmacological identification of dopamine D2-receptors in the rabbit carotid body.

Dopamine D2-receptors were directly identified in receptor binding assays with washed particulate preparations of rabbit carotid body using the selective ligand, [3H]domperidone. High affinity, saturable specific binding of [3H]domperidone was clearly demonstrable and chronic section of the sinus nerve resulted in a 32% decrease in the labelling of the dopamine D2-sites. Adenylate cyclase activity was also detected in rabbit carotid body homogenates and although this enzyme was stimulated 4-fold by 10 mM sodium fluoride, neither dopamine nor isoprenaline significantly altered basal activity. On the other hand, in the intact carotid body incubated in vitro, 10(-5) M isoprenaline increased the basal cyclic AMP content 6-fold, though dopamine was again ineffective. The effect of various selective dopamine receptor antagonists and agonists was also studied on chemoreceptor afferent discharge. The results confirm that depression of 'spontaneous' chemosensory discharge is the predominant effect of dopamine (0.01-100 micrograms) in rabbits. The 'selective' D2-agonist, LY 141865, proved very effective (ID50 3.3 nmol) and was equipotent with dopamine (ID50 4.2), whereas, the D1-agonist, SK & F 38393, was very ineffective (ID50 150). The D2-antagonists domperidone and (-)-sulpiride produced a dose-related decrease in the chemodepressant responses to dopamine and LY 141865. However, there was no evidence for any appreciable excitatory action of either of these agonists after blockade of their chemo-depressant effects. The D2-antagonists variably affected the spontaneous activity, there being an increase in discharge on average, whereas responses to hypoxia, cyanide and CO2 were reduced. The present results from biochemical and neuropharmacological studies, provide strong evidence for the presence of functional dopamine D2-receptors in the rabbit carotid body, and suggest that the receptor involved in dopamine-induced depression of chemosensory discharge is of D2-type.